Researchers at MIT have found that the genome's three-dimensional structure does not fully disappear during cell division, as long believed. Instead, small loops known as microcompartments remain intact and even strengthen, potentially explaining brief gene activity surges in mitosis. This discovery challenges traditional views of how cells maintain genetic regulation across divisions.
For decades, scientists assumed that during mitosis—the phase of cell division where chromosomes condense and duplicate—the genome's intricate 3D architecture temporarily vanishes, only to reform afterward. This model suggested a 'blank slate' with no gene-related structure, allowing for a clean reset of genetic activity.
New findings from MIT, published in Nature Structural and Molecular Biology, upend this idea. Using a high-resolution mapping technique called Region-Capture Micro-C (RC-MC), developed by the team in 2023, researchers identified 'microcompartments'—tiny loops connecting enhancers (regulatory DNA segments) to promoters (gene starting points). These loops persist through mitosis, becoming more pronounced as chromosomes compact.
"This study really helps to clarify how we should think about mitosis. In the past, mitosis was thought of as a blank slate, with no transcription and no structure related to gene activity. And we now know that that's not quite the case," said Anders Sejr Hansen, an associate professor of biological engineering at MIT.
The strengthening loops may help cells 'remember' pre-division genetic interactions, bridging genome structure to function—a longstanding challenge in the field. Lead author Viraat Goel PhD '25 noted, "The findings help to bridge the structure of the genome to its function in managing how genes are turned on and off, which has been an outstanding challenge in the field for decades."
This persistence also sheds light on a mysterious transcriptional burst observed since the 1960s, with spikes confirmed in 2016 and 2017 studies. Microcompartments near active genes form accidentally due to compaction, briefly activating transcription before the cell prunes them in the G1 phase post-division.
Senior authors include Hansen and Edward Banigan, with co-authors Leonid Mirny of MIT and Gerd Blobel of the University of Pennsylvania. The work, funded by the NIH and others, opens questions on how cell size and shape influence these structures.